tbuckley/cabot-search huggingface dataset:
Trends in overall survival in 133 cases of balloon cell melanoma: An NCDB analysis.
Authors: Xinxin Wu, Darby Keirns, Beau Hsia, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2023)

e21508 Background: Balloon cell melanoma (BCM) is a rare, malignant subtype of melanoma characterized by large, foamy melanocytes lacking pigmentation with a low overall 5-year survival rate of 37.5%. The incidence of melanoma is increasing at a greater rate than other types of cancer, but the cases of this subtype remain low. Demographic factors were analyzed via the National Cancer Database (NCDB) in an attempt to mitigate the knowledge gap in BCM diagnoses. The primary site at presentation and the effects of demographic factors on overall survival are described. Methods: A retrospective cohort analysis utilizing the NCDB from 2004 to 2020 included patients diagnosed with histologically confirmed BCM (N = 133). Socio-demographic factors (sex, age at diagnosis, race, facility type, and insurance type) were analyzed for frequency. A multivariate analysis of factors was performed on overall survival via the Kaplan–Meier Method (p = 0.05). Results: Since 2004, the number of cases diagnosed with BCM has steadily decreased (R2 = 0.204). The average age at diagnosis was 58.17 years (SD = 17.3). Most patients were male (63.9%), White (94.0%), treated at a non-academic center (56.4%), and had government insurance (96.1%). On multivariate analysis, age, race, and insurance type had statically significant effects on overall survival (p &lt; 0.001). Patients that were older at diagnosis had poorer overall survival (p &lt; 0.001, CI = [1.022 - 1.075]). Black patients were 4.6 times more likely than White patients to have suffered death (p &lt; 0.001, CI = [23.586 - 450.230]). Patients without insurance were more likely to die than patients with government insurance (p &lt; 0.001, CI = [0.026 - 0.229]). The average time from diagnosis until death was 143.1 months (SD = 8.0) with a 1-year and 5-year survival rate of 92.0% and 72.2%, respectively. Conclusions: This is the first study analyzing trends and demographic features relating to BCM in the NCDB. Due to the low survival rate of this cancer, understanding the risk factors affecting overall survival serve as a valuable clinical tool for prognostic evaluation. This database analysis suggests that the survival rate of BCM might be higher than previous literature suggests. The differences in BCM treatment on overall survival were not described in this study. Future research should aim to evaluate other prognostic factors, such as treatment, on survival.
Integration of breast-oncology clinical pathways in Providence Southern California clinical research network.
Authors: Parvin F. Peddi, Thomas Bott, Nanor Bozoyan, Trisha Babcock, Kristen Cushman, Santosh Kesari
Journal: Journal of Clinical Oncology (2023)

e18710 Background: ClinicalPath is an evidence-based oncology decision support and analytics tool for cancer care. ClinicalPath’s treatment recommendations are prioritized based on efficacy, toxicity, and cost by a nationwide committee of oncologists. The pathways are updated quarterly and are expected to speed the integration of new treatments into practice, standardize therapy, improve quality, and decrease cost. The pathway system also allows for local clinical trial mapping to promote clinical trial awareness and increase enrollment. ClinicalPath provides clinical pathways delivering personalized, evidence-based oncology guidance at the point of care. ClinicalPath’s network in North America serves more than 2,000 cancer physicians, within 54 practices in 31 states (15 academic medical centers, 29 hospital systems, and 9 community practices). Methods: Providence’s Population: Our population is derived from multiple hospitals in Southern California within the Providence Health System. Methodology: Medical oncologists and Advanced Practice Providers received training on ClinicalPath before go-live. ClinicalPath was integrated into the Epic EHR in multiple Southern CA hospitals in a single month. Results: After 4 months of utilization within our Southern California region, 342 treatment decisions were made across all cancers, and 85.1% of cancer patients were treated on pathway. Of which, 103 treatment decisions were made within the breast-oncology specialty, and 93.2% of those cancer patients were treated on pathway. Conclusions: We successfully integrated and initiated ClinicalPath in a multiple hospital-affiliated community oncology clinical trial network. We are actively working across our Southern California Region to map locally available clinical trials to promote awareness and increase enrollment. Provider utilization and patient on-pathway rates are actively monitored.
Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004.
Authors: Tanya Siddiqi, David G. Maloney, Saad Kenderian, Danielle M. Brander, Kathleen Anne Dorritie, Jacob Soumerai, Peter A. Riedell, Nirav Niranjan Shah, Rajneesh Nath, Bita Fakhri, Deborah Marie Stephens, Shuo Ma, Tatyana A Feldman, Scott R. Solomon, Stephen J. Schuster, Serena K. Perna, San-San Ou, Eniko Papp, Yizhe Chen, William G. Wierda
Journal: Journal of Clinical Oncology (2023)

7501 Background: In patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based regimens, achieving CR with current treatment is uncommon. New therapies that achieve deep and durable responses are needed. We report the primary analysis of the phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study evaluating liso-cel in pts with R/R CLL/SLL. Methods: Pts must have received at least 2 prior lines of therapy, including a BTKi. Eligible pts received liso-cel at a target dose of either 50 (DL1) or 100 (DL2) × 10 6 CAR + T cells. The primary endpoint was rate of CR and CR with incomplete marrow recovery (CRi) by IRC per 2018 iwCLL criteria in the prespecified subset of efficacy-evaluable pts with disease progression on BTKi and ven failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H 0 ]: ≤ 5%). Key secondary endpoints were ORR (H 0 : ≤ 40%) and rate of undetectable minimal residual disease (uMRD; 10 −4 ) in blood (H 0 : ≤ 5%). Results: Of 137 leukapheresed pts, 117 received liso-cel (safety set), 96 (DL1 = 9; DL2 = 87) were efficacy evaluable, and 53 (DL1 = 4; DL2 = 49) were in the PEAS. In the safety set, median (range) age was 65 y (49–82), 83% had high-risk features, median (range) lines of prior therapy was 5 (2–12), and all pts had prior BTKi. Median (range) on-study follow-up was 21.1 mo (0.4–55.6) for the safety set. In the PEAS at DL2, the primary endpoint of CR/CRi rate was met at 18.4% (95% CI, 8.8–32.0; 1-sided P = 0.0006; Table). ORR was 42.9% and was not statistically significant (95% CI, 28.8–57.8; 1-sided P = 0.3931). The uMRD rate was 63.3% in blood and 59.2% in marrow. Median (95% CI) DOR was 35.3 mo (11.01–not reached [NR]) with a median follow-up of 19.7 mo. Median duration of CR/CRi was NR. In the safety set, rate of any-grade CRS was 84.6% (gr 3, 8.5%; no gr 4/5) and neurological events (NE) was 45.3% (gr 3, 17.9%; gr 4, 0.9%; no gr 5); 69.2% received tocilizumab and/or corticosteroids for CRS/NEs. Rate of gr ≥ 3 infections, hypogammaglobulinemia, and prolonged cytopenia was 17.1%, 15.4%, and 53.8%, respectively. One death related to liso-cel was due to hemophagocytic lymphohistiocytosis. Liso-cel exhibited rapid in vivo expansion and was detected by qPCR in blood up to 36 mo after infusion. Conclusions: Liso-cel demonstrated durable CR/CRi, high uMRD rates, and a manageable safety profile in pts with heavily pretreated, high-risk R/R CLL/SLL and high unmet need. Clinical trial information: NCT03331198 . [Table: see text]
Clinical efficacy of frontline immunotherapy (IO) in ethnic-minority patients (pts) with metastatic NSCLC.
Authors: Matthew Lee, Jianyou Liu, Emily Miao, Shuai Wang, Frank Zhang, John X Wei, Julie Chung, Xiaonan Xue, Balazs Halmos, Dean Hosgood, Haiying Cheng
Journal: Journal of Clinical Oncology (2023)

e21063 Background: Since minority pts have been historically underrepresented in key IO trials, knowledge on the clinical use of IO in ethnic-minority pts with non-small cell lung cancer (NSCLC) remains limited. This study aims to evaluate race/ethnicity and other demographic, socioeconomic and clinical factors of pts with metastatic NSCLC treated with first-line IO. Methods: A retrospective cohort study of 5920 pts diagnosed with lung cancer within the Montefiore Health system from 1/1/2013 to 6/1/2022 was conducted. Pts with metastatic NSCLC without EGFR or ALK alterations and underwent first-line IO use were identified. The primary endpoint was overall survival (OS) with secondary endpoints of progression-free survival (PFS) and time to discontinuation (TTD) from the start of IO. Results: In total, 248 pts were identified with median follow-up time of 10.7 months (mons), median age of 66 years and 39.1% as Non-Hispanic Black (NHB), 30.2% as Hispanic and 30.7% as non-Hispanic White (NHW). OS (p = 0.39), PFS (p = 0.29) and TTD (p = 0.98) were similar among races/ethnic groups. ECOG &lt; 2 at the start of IO was associated with longer OS summarized in Table 1. Significantly higher PFS and TTD were noted respectively in pts with Medicare insurance and PD-L1 status (TPS&gt;1), while lower PFS and TTD with lower BMI. These results were remained after adjusting for biological sex, smoking status, histology, and IO regimen. Conclusions: Our study demonstrates that race/ethnicity does not impact the benefits of IO. However, factors such as ECOG status impact OS, and BMI, insurance and PD-L1 significantly impact PFS and TTD. These findings help identify potential factors that can be addressed to optimize outcomes and supportive care while undergoing IO.[Table: see text]
Stage 4N neuroblastoma before and during the era of anti-GD2 immunotherapy.
Authors: Brian H. Kushner, Shakeel Modak, Michael P. LaQuaglia, Ellen M. Basu, Justin T Gerstle, Fiorella Iglesias Cardenas, Kim Kramer, Stephen S. Roberts, Suzanne L. Wolden, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2023)

10037 Background: Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high-risk neuroblastoma (HR-NB) before myeloablative therapy (MAT) and immunotherapy with anti-GD2 monoclonal antibodies (mAb) became standard. No report presents results with contemporary treatment programs for 4N. The only large study to date (from the International Neuroblastoma Risk Group) analyzed patients diagnosed 1990-2002, found 4N to have significantly better event-free (EFS) and overall survival (OS) compared to other stage 4 patients, and recommended considering less intensive therapy for 4N. Methods: We conducted a retrospective analysis of patients treated at our center from 1985-2021 to analyze our large experience to fill the gap in the literature on treatment of 4N, namely, results with contemporary multi-modality therapy including MAT and anti-GD2 mAbs. Results: We found and reviewed 48 pediatric 4N patients ( &lt; 18 years old) treated 1985-2021 at our center. Biological features included segmental chromosomal aberrations in 21/21 MYCN-non-amplified patients, mutations of ALK in 4/22 (18%), ATRX in 4/16 (25%), and TERT in 4/12 (33%) patients. Among 33 MYCN-non-amplified high-risk patients ( &gt; 18 months old), 19 are relapse-free 1.6+-to-36.9+ (median 12.2+) years post-diagnosis, including 13 without prior MAT and 3 with no mAb, while 14 patients (7 without prior immunotherapy) relapsed (all in soft tissue initially). Eleven of the 14 died, including 3 who developed late osteomedullary metastases after 3-5 relapses in soft tissue alone. Of 13 MYCN-amplified 4N patients, 6 are relapse-free 4.5+-to-25.8+ (median 11.7+) post-diagnosis (all received mAbs; 3 underwent MAT) and 3 are in 2nd remission 4.4+-to-21.1+ years post-relapse (all soft tissue). For all high-risk 4N patients, 5/10-year EFS was 55%/52%, and OS was 76%/64%. MAT was not prognostic. The 2 patients with intermediate-risk 4N (14 months old) are relapse-free 7+ years post-resection of primary tumors; distant disease spontaneously regressed. Conclusions: The natural history of 4N is marked by NB confined to soft tissue without early relapse in bones or bone marrow, sites where mAbs have proven efficacy. These findings plus the possibility of survival without MAT and/or mAb immunotherapy, as seen elsewhere and at our center, support consideration of treatment reduction for selected MYCN-non-amplified 4N patients.
Tumor immune microenvironment (TIME) analysis of stage I lung adenocarcinoma with micropapillary pattern.
Authors: Yun Han, Yue Yu, Chongyuan Xu, Qianru He, Qin Zhang, Tingting Sun, Chuang Qi
Journal: Journal of Clinical Oncology (2023)

e20510 Background: Micropapillary is one of the most aggressive histologic subtypes of lung adenocarcinoma, which is considered a poor prognostic marker. Comprehensive analysis of tumor immune microenvironment (TIME) features of micropapillary of early invasive lung adenocarcinoma may provide better insight and facilitate the development of novel strategies for early detection and intervention. Methods: A total of 15 patients who underwent anatomical resection and were pathologically diagnosed with stage I micropapillary adenocarcinomas were included in this study. Gene expression profiles (GEPs) of tumor immune-related 289 genes were analyzed using NanoString nCounter. Differentially expressed genes(DEGs), estimation of TIME cell infiltration, and TIME signatures between micropapillary and non-micropapillary were assessed. Results: The number of micropapillary and non-micropapillary patients was 5 and 10. The comparison revealed CD69, IL6, CXCL8, CXCL2, POLR2A and so on were significantly upregulated in the micropapillary group compared with the non-micropapillary group, while HLA-DPA1, IFIT2, and other seven genes were down-regulated in the micropapillary group. These DEGs were mostly enriched in “positive regulation of cytokine production”， “T cell activation”， “receptor ligand activity，” and “signaling receptor activator activity” pathways according to GO enrichment analysis. The results of the KEGG analysis revealed that genes were significantly enriched in “IL-17 signaling pathway”, “TNF signaling pathway”, “cytokine-cytokine receptor interaction”, and so on. Meanwhile, different immune infiltration of the two groups was analyzed. Totally, there was a better TIME cell infiltration in the micropapillary group compared with the non-micropapillary group. Especially, the score of DCs and mast cells was significantly higher in micropapillary group. However, TIME signature scores were similar in both groups. Conclusions: Our study demonstrated that the TIME between micropapillary and non-micropapillary of stage I lung adenocarcinoma was different. Increased mast cells explained poor prognosis in lung adenocarcinoma with micropapillary pattern. A high level of DCs infiltration indicated that micropapillary adenocarcinoma might benefit from immunotherapy.
ctDNA for clonal evolution surveillance and therapeutic efficacy prediction in unresectable locally advanced non-small cell lung cancer under radiotherapy.
Authors: Nan Bi, Yufan Yang, Jianyang Wang, Jingbo Wang, Xiaotian Zhao, Yin Yang, Minyi Zhu, Luhua Wang
Journal: Journal of Clinical Oncology (2023)

e20555 Background: Therapeutic efficacy differs across unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive radiotherapy/chemoradiotherapy (RT/CRT), but the underlying resistance mechanism, clonal evolution and molecular prognostic factors remain poorly understood. Methods: Unresectable LA-NSCLC patients treated with definitive RT/CRT were consecutively enrolled between May 2018 and November 2020. Next-generation sequencing covering 474 cancer-relevant genes was performed on plasma ctDNA collected at pre-treatment (TP0), 4-week post-RT (TP1), 1-month post-RT (TP2), 3-month post-RT (TP3), and progression (TP4). Main study endpoints included disease progression, progression-free survival (PFS), death from any cause, overall survival (OS), distant metastasis and distant metastasis free survival. Fisher’s exact test and two-sample t-tests were performed to compare the frequencies and means of independent groups, respectively. The median follow-up time was estimated using the reverse Kaplan-Meier method. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards models. Results: A total of 46 patients were included (median age: 63 [range: 40–80], males: 87%, clinical stage IIIB: 52%, squamous cell carcinoma: 54%, TP0 ctDNA shedding: 63%, consolidation immunotherapy: 33%). Twenty-nine (63%) patients developed disease progression by the end of follow-up (median follow-up: 23.7 months), with median PFS and OS being 15.5 and 25.4 months, respectively. The polymerase epsilon ( POLE) mutational signature at TP0 indicated inferior PFS (HR: 5.32, 95% CI: 1.83–15.45) and worse OS (HR: 20.68, 95% CI: 3.94–108.62). Notably, newly-discovered/lost mutations were rarely observed at TP4 when compared to TP0. Patients with a high ratio of mean over max variant allele frequency (m/mVAF) in TP0 samples, indicative of a clonal predominant tumor with a low subclone fraction ( P&lt; 0.01), had relatively poor OS, compared to patients with low m/mVAF (HR: 2.92, 95% CI: 0.82–10.46) or undetectable ctDNA (HR: 3.39, 95% CI: 0.98–11.75). The prognostic value was validated in an independent publicly available dataset of 431 LA-NSCLC patients receiving definitive RT/CRT, showing patients with high m/mVAF demonstrated worse OS than those with low m/mVAF (HR: 1.43, 95% CI: 1.08–1.89). Additionally, increased m/mVAF between TP0 and TP1 indicated an elevated risk for disease progression ( vs. non-increase, HR: 3.49, 95% CI: 1.20–10.16), especially for distant metastasis ( vs. non-increase, HR: 2.85, 95% CI: 0.84–9.69). Conclusions: Our findings demonstrated the clinical value of plasma ctDNA and its derived molecular features in delineating clonal evolution, monitoring therapeutic resistance, and predicting prognosis of LA-NSCLC under definitive RT.
New concept infusion pump with an anticancer drug exposure prevention function.
Authors: Akihito Tsuji
Journal: Journal of Clinical Oncology (2023)

e18722 Background: In recent years, cancer chemotherapy has taken measures to prevent exposure to anticancer drugs. Major exposure prevention measures include the use of safety cabinets and closed dispensing devices during preparation, closed infusion sets, and patient education to avoid exposure to the surrounding environment, such as through defecation. On the other hand, the closed circuit needs to be opened after the continuous infusion pumping of anticancer drugs, and the risk of exposure to anticancer drugs during this process remains an issue. In response to this issue, we aimed to develop a pump with an anticancer drug exposure prevention function. Methods: We designed a pump for the continuous infusion of anticancer drugs equipped with an additional circuit in the pump vessel for root flushing and heparin lock without opening the closed circuit. The additional circuit was connected downstream of the continuous infusion flow control mechanism to allow the circuit to be flushed without opening the closed circuit. Results: We successfully developed a continuous infusion pump (PCT/JP2020/017083) with anticancer drug exposure protection. Our newly developed hexagonal cylindrical pump (length: 6 cm; width: 6 cm; height: 13.5 cm) is portable, lightweight (70 g), has a maximum capacity of 85 mL, and allows 46-h continuous infusion of anticancer drugs such as FOLFOX, FOLFIRI, FOLFOXIRI, and FOLFIRINOX. The port for flushing is covered with a sterile seal to keep it clean until use. Our new pump eliminates the risk of releasing routes filled with anticancer drugs and prevents unnecessary exposure to anticancer drugs by handlers such as health-care professionals, patients, family members, and caregivers. Furthermore, the risk of infection is reduced as the system can be cleaned while closed. Conclusions: Our newly developed infusion pump with an anticancer drug exposure prevention function may help enable the next generation of cancer drug exposure prevention measures. Support: Japan Agency for Medical Research and Development, Medical Innovation Project, Development and Commercialization Project (Adoption No.: 21he0122019j000).
Patient-reported outcomes of furmonertinib versus gefitinib in patients with locally advanced or metastatic, <i>EGFR</i> mutation-positive non-small cell lung cancer (FURLONG): A multicenter, double-blind, randomized phase 3 study.
Authors: Yuankai Shi, Gongyan Chen, Xiang Wang, Yunpeng Liu, Lin Wu, Yanrong Hao, Chunling Liu, Shuyang Zhu, Xiaodong Zhang, Yuping Li, Jiwei Liu, Lejie Cao, Ying Cheng, Hui Zhao, Shucai Zhang, Ai-min Zang, Jiuwei Cui, Jian Feng, Nong Yang, Jie Hu
Journal: Journal of Clinical Oncology (2023)

9081 Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), along with an acceptable safety profile without new signals in the FURLONG study. Here we present patient-reported outcomes (PROs). Methods: FURLONG is a multicenter, double-blind, double dummy, randomized phase 3 study done in 55 hospitals across mainland China. Eligible patients were randomly assigned (1:1) to receive either furmonertinib or gefitinib. The primary endpoint of IRC-assessed progression-free survival has been reported previously. PROs as prespecified secondary outcomes by the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13), were analyzed in randomly assigned patients who had received at least one dose of study drug and completed at least one PRO assessment. Changes from baseline to randomized treatment discontinuation were analyzed with mixed model for repeated measures and time-to-event analyses. This study is ongoing for survival follow-up. Results: 357 patients received at least one dose of study drug, all of them completed at least one PRO assessment. Questionnaire completion rates were ≥95% at most time points. Baseline mean scores were similar in the furmonertinib and gefitinib groups. From baseline to randomized treatment discontinuation, statistically significant differences favoring furmonertinib for physical function, nausea/vomiting, appetite loss, diarrhea, alopecia, and other pain (any pain other than chest, arm, or shoulder pain) were observed. Time to deterioration in physical function, cognitive function, nausea/vomiting, appetite loss, diarrhea, cough, dyspnea, dysphagia, and alopecia were significantly longer with furmonertinib versus gefitinib (Table). Conclusions: Furmonertinib demonstrated favorable PROs as measured by the EORTC QLQ-C30 and QLQ-L13 versus gefitinib. These data presented the positive benefit risk profile of first-line furmonertinib and further support this novel third generation EGFR-TKI as a new standard of first line treatment in EGFR mutation-positive NSCLC. Clinical trial information: NCT03787992 . [Table: see text]